Adding radiation to hormone therapy slows progression of oligometastatic prostate cancer
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Adding localized radiation therapy to intermittent hormone therapy extended PFS among men with oligometastatic prostate cancer, data from the randomized phase 2 EXTEND trial showed.
Results of the basket trial, presented at American Society for Radiation Oncology Annual Meeting, suggest that metastasis-directed radiation therapy can help slow disease progression while allowing patients to take breaks from receiving hormone therapy, the investigators noted.
Background
Multiple studies have shown a synergistic ability of radiation therapy to improve outcomes in men receiving hormone therapy for prostate cancer, according to Chad Tang, MD, associate professor of radiation oncology at The University of Texas MD Anderson Cancer Center.
“We also know from previous studies that upfront hormone therapy has been associated with improvements in overall survival,” he said during the presentation. “However, hormone therapy has been associated with adverse effects, and men with prostate cancer who have been treated with this therapy generally hate it and it is a big detriment to their quality of life.”
Regardless, intermittent hormone therapy has a questionable track record based on a previous study that may not have been entirely applicable to patients with oligometastatic prostate cancer, Tang noted. This prompted his group to evaluate an intermittent strategy in combination with localized radiation therapy to limit exposure to hormone therapy and determine its impact on disease progression.
Methodology
The EXTEND trial enrolled patients with multiple solid tumors to evaluate whether metastasis-directed radiation therapy prolonged PFS when added to intermittent hormone therapy.
Tang and colleagues designed the EXTEND intermittent prostate cancer basket, which enrolled 87 men with oligometastatic prostate cancer — defined as five or fewer metastases — who underwent random assignment to combined metastasis-directed radiotherapy plus intermittent hormone therapy (n = 43) or intermittent hormone therapy alone (n = 44).
Participants initially received at least 2 months of hormone therapy and continued receiving hormone therapy after assignment to a study group. Hormone therapy comprised a luteinizing hormone-releasing hormone agonist or antagonist with or without a second-generation androgen-receptor targeting agent.
A planned break from hormone therapy took place 6 months after enrollment. The study withheld hormone therapy until disease progression occurred.
PFS — defined as death or radiographic, clinical or biochemical disease progression — served as the study’s primary endpoint. A secondary endpoint included time that eugonadal patients maintained normal testosterone levels — defined as greater than 150 ng/dL — until disease progression.
Investigators determined PFS to have occurred at 41 independently assessed and reported events, which occurred at median follow-up of 22.1 months (range, 13-39.3).
Key findings
Median PFS significantly improved with the addition of metastasis-directed radiation therapy to hormone therapy compared with hormone therapy alone (not reached vs. 15.8 months; HR=0.25; 95% CI, 0.12 to 0.55).
Combination therapy also significantly improved the median time eugonadal patients maintained normal testosterone levels until disease progression compared with hormone therapy alone (not reached vs. 6.1 months; P= .03).
Further analysis showed that the time to appearance of new lesions significantly improved in the combination therapy group, with a 2-year rate of 33% compared with 41% among those who received hormone monotherapy (P = .04).
Three grade 3 treatment-related toxicities occurred in both treatment groups.
Clinical implications
The results demonstrate that metastasis-directed radiation therapy combined with intermittent hormone therapy improved PFS and the amount of time patients could stay off hormone therapy, Tang noted.
“Importantly, for men, metastasis-directed therapy combined with hormone-directed therapy also improved time with [normal] testosterone levels, something they can all enjoy,” he told the audience. “Intermittent hormone therapy in combination with metastasis-directed radiation therapy may facilitate prolonged [normal] testosterone intervals while maintaining excellent disease control in men with oligometastatic prostate cancer.”
Perspective
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Jay Ciezki, MD
Tang and colleagues presented results of the prostate cancer cohort of the EXTEND trial, which included patients with oligometastatic prostate cancer. In this cohort, systemic hormonal manipulation occurred at the initiation of the trial with a break planned at 6 months after its initiation. Patients were required to have five or fewer sites of treatable disease. Two months after initiation of hormonal manipulation, researchers randomly assigned patients to metastasis-directed radiation therapy or observation.Results showed longer median PFS in the metastasis-directed radiation therapy group vs. observation (not reached vs. 15.8 months; P < .001). In addition — and very importantly — investigators assessed time from eugonadal testosterone levels to progression in the metastasis-directed radiation therapy group vs. observation (median, not reached vs. 6.1 months, P = .03). Researchers reported three grade 3 toxicities in each arm.
The concept of treating oligometastatic prostate cancer with local intensification via radiation therapy is not new. The antecedent STOMP and ORIOLE trials confirm the improvement in PFS with metastasis-directed radiation therapy. The results of EXTEND show that with this regimen, patients not only benefit in terms of PFS but also were able to do so with a longer time with eugonadal testosterone levels. Although not specifically mentioned in the presentation, one may assume that this prolongation of eugonadal status improved patients’ quality of life. PFS in metastatic prostate cancer is an important endpoint, but quality of life is equally so. EXTEND shows us that improved PFS is possible with improved quality of life.
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Tang C, et al. Abstract LBA 05. Presented at: American Society for Radiation Oncology Annual Meeting; Oct. 23-26, 2022; San Antonio.
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